1. Field of the Invention
This invention relates to a stopper for a container and, more particularly, to an improved stopper for a container of parenteral solutions which is suitable for infusion spike penetration without producing unacceptable amounts of particulate matter.
2. Reported Developments
Stopper systems for vials, bottles and the like are made of materials that are resistant to chemicals and pharmaceuticals such as corrosive materials, reagents, parenteral solutions and solid formulations reconstitutable with a solvent prior to use. The most commonly used stopper system for such products has been glass or plastic bottles and vials equipped with rubber stoppers made of elastomeric materials. The system appears to provide for good hermetical seal, safe storage and easy access to the content through the elastomeric stopper via the use of an infusion spike when withdrawal of the content is desired. The elastomeric stopper used comprises an elastomeric base, such as natural or synthetic rubber and an inert coating covering at least some portions of the stopper. The coating used heretofor includes chlorobutyl rubber, polymeric fluorocarbon resins such as polytetrafluoroethylene (TEFLON) and various thermoplastic films. The coating is intended to insulate the elastomeric stopper base from the content of the container in order to prevent contact and possible chemical reactions therebetween.
One of the major concerns in all products, and especially pharmaceutical parenteral products, is the generation of particulate foreign matter which may contaminate such products. In order to eliminate macroscopic and microscopic particulates, elaborate measures have been taken to remove them, such as filtration of the product and special washing and drying of the stopper system components. These steps help assure that the products meet the requirements and guidelines of the pharmaceutical industry, such as compendia guidelines, when the products reach the point of use. However, at the point of use, such as in the case of a parenteral product, new particulate matter is frequently generated by the practitioner when the stopper is penetrated by a needle or spike of an infusion set or an infusion spike. During such penetration a combination of elastic and plastic deformation of the stopper target area increases the stopper contact surface with the infusion spike as it is pressed into the stopper. Typically, untreated elastomeric stoppers offer a high degree of resistance against the exterior surface of the spike as the spike is being pushed into the penetration area. Most frequently, when stopper fragments are generated, they are the result of the elastomeric portion of the stopper being abraded off the upper surface of the stopper as it conforms to the shape of the penetrating spike. The fragments are then transported into the interior of the vial as the spike rolls and drags the fragments during penetration.
In addition to the problem of particulate matter produced and carried into the vial during the spiking procedure, there are two other, although less frequently occurring, anomalies: stopper push-through into the vial and spike blow-out caused by residual elastic tension of the stopper against the spike which urges the spike outward.
The most common solution to these problems has been the application of silicone lubricant to the stopper and/or the spike to reduce the frictional drag between the stopper and the spike. While silicone does reduce particle generation from the spiking procedure, it also increases the risk of product contamination from its own composition.
Another approach proposed in the prior art to reduce the tendency of the stopper to generate particulate matter during manufacturing and storage is to coat the elastomeric core of the stopper with a thermoplastic film on the fluid contacting side thereof. We have found, however, that the use of such construction is less than satisfactory to solve the problem: the elastomeric particles generated by the spike during the piercing process are carried into the vials equipped with such stoppers.
The present invention addresses the need to eliminate or at least greatly reduce the particle generation from surface erosion of the stopper during spike penetration. In addition, the invention reduces the risk of the push-through and blow-out tendency by minimizing frictional drag and residual elastic tension during spike penetration. These advantages are achieved without the use of a lubricant, such as silicone oil, which could contaminate the product contained in the vial or bottle.